STABIL Study: National Study With Mircera for Maintenance of Hemoglobin Level in Dialysis Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for STABIL Study: National Study With Mircera for Maintenance of Hemoglobin Level in Dialysis Patients (NCT00642850), a na phase 3 study. The primary outcome is Percentage of Participants Maintaining Average Hemoglobin Concentration Within +/-1 Gram Per Deciliter (g/dL) of Reference and Within the Target Range.

2. Clinical Question

The reference hemoglobin value was based on five assessments during the Stability Verification Period, at Weeks -4, -3, -2, -1 and 0. The endpoint therefore concerns stability relative to each participant’s own reference as well as remaining within a specified hemoglobin range. It is a measure of maintenance during the efficacy evaluation period, not a comparison of change against a control group.

The study title and summary frame the question around maintenance during monthly C.E.R.A. administration. Because there was one treatment group, the design can describe outcomes among participants who received the intervention, but it cannot by itself establish how those outcomes would compare with another treatment or with no treatment. The registry record does not report a primary endpoint result.

3. Trial Design

The STABIL Study is listed as a Phase 3, single-arm, open-label study. Its allocation is recorded as not applicable, and masking is recorded as none. These design features mean that the registry does not describe random assignment between groups or blinded treatment assessment. Enrollment was 188 participants, and the study status is completed.

Participants received monthly intravenous C.E.R.A. The brief summary describes a starting dose of 120, 200 or 360 micrograms, selected according to the epoetin dose administered in the week before the first study drug administration. The anticipated time on study treatment was 3-12 months. These are descriptions of the planned treatment approach; the registry record does not report individual treatment duration or the number of participants who received each starting dose.

The primary endpoint was assessed from Week 17 up to Week 24. It combined two conditions: the participant’s time-adjusted average hemoglobin had to be within +/-1 g/dL of the reference hemoglobin value and between 10.0 and 12.0 g/dL during the efficacy evaluation period. The reference was based on measurements during the Stability Verification Period at Weeks -4, -3, -2, -1 and 0.

The registry record lists secondary outcomes concerning hemoglobin change, time in the target range, dose adjustment, red blood cell transfusion, and anti-epoetin antibodies. It lists seven outcome measures in total, while the secondary outcome descriptions name six measures. No analysis records are listed. The record does not report a randomized comparator, a formal statistical analysis plan, or the actual primary endpoint estimate.

A single-arm design is useful for describing observed outcomes under a treatment regimen, but it does not separate treatment-associated changes from other influences over time. Open-label conduct also means participants and study staff were not masked to treatment. Those design characteristics matter when interpreting outcome assessments, especially when no concurrent comparison group is available.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per protocol (PP) population included all participants in the safety population with the exception of participants with less than 3 recorded hemoglobin values, missing administrations of C.E.R.A., withdrawal, inadequate iron status in Weeks 16-24.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: The safety population was defined as all participants enrolled into the study.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Maintaining Average Hemoglobin Concentration Within +/-1 Gram Per Deciliter (g/dL) of Reference and Within the Target Range, measured over Week 17 up to Week 24.

The primary endpoint is the percentage of participants whose average hemoglobin concentration during the efficacy evaluation period met both a relative and an absolute criterion. The relative criterion was within +/-1 g/dL of the participant’s reference hemoglobin value. The absolute criterion was within the target range of 10.0 to 12.0 g/dL. The evaluation period ran from Week 17 up to Week 24.

The reference value was based on five hemoglobin assessments recorded during the Stability Verification Period at Weeks -4, -3, -2, -1 and 0. The mean during the efficacy evaluation period was estimated as a time-adjusted average for each participant. This approach makes the endpoint about maintaining hemoglobin, rather than simply recording a single measurement at one visit. The endpoint also requires the average to satisfy both criteria; meeting only the relative criterion or only the target-range criterion would not meet the stated definition.

As a general statistical point, a binary percentage is a compact way to describe the proportion of a defined population that meets an outcome rule. The rule must be interpreted alongside the analysis population and the handling of missing measurements, because both affect which participants contribute to the estimate. Here, the registry describes a per-protocol population and lists exclusions, but does not report the endpoint percentage or its 95% confidence interval. The endpoint’s intended interpretation is clear, while its observed magnitude and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-arm design estimate?

As a general statistical point, a single-arm study estimates outcomes in a group receiving the study intervention. It does not estimate a randomized difference between treatment groups because no concurrent comparator group is described in this registry record. The STABIL Study is listed as single-group, with allocation not applicable and no masking. Its primary endpoint therefore concerns the proportion meeting the maintenance definition among the defined analysis population, rather than a between-group treatment effect.

A participant’s reference hemoglobin value provides an internal point of comparison for the endpoint. This can describe whether measurements during the efficacy evaluation period stayed near that reference. It does not control for all influences that could change over time. In general, a concurrent comparison group helps distinguish changes associated with the intervention from changes that might have occurred for other reasons. No such randomized comparison is reported.

How should the percentage endpoint be read?

The primary outcome is binary at the participant level: each participant either meets the endpoint definition or does not, and the result is expressed as a percentage. The definition requires the time-adjusted average hemoglobin from Week 17 up to Week 24 to be within +/-1 g/dL of the reference value and within 10.0 to 12.0 g/dL. Because both conditions must hold, the percentage represents participants meeting the combined rule, not separate percentages for each condition.

As a general statistical point, percentages depend on a denominator. The registry defines the primary analysis population as per protocol and describes exclusions from the safety population, but does not report the final denominator or the number meeting the endpoint. The enrollment count of 188 is not necessarily the denominator for the primary analysis. The actual percentage and its 95% confidence interval are not reported in the registry record.

What does the confidence interval contribute?

The endpoint lists a 95% confidence interval as its measure of dispersion. As a general explanation, a confidence interval conveys uncertainty around an estimate under the method’s assumptions. It is not a guarantee about an individual participant’s outcome, and its width is relevant to how precisely the underlying proportion has been estimated. Since neither the endpoint estimate nor the interval limits are reported, the precision of this primary result cannot be assessed from the registry record.

The record does not state which method was used to calculate the interval. It also does not report whether any adjustment was applied to the estimate. Those details should not be inferred from the fact that an interval was planned or listed as the dispersion measure.

Why do the population rules matter?

The per-protocol population excludes participants in the safety population who had fewer than 3 recorded hemoglobin values, missing administrations of C.E.R.A., withdrawal, or inadequate iron status during Weeks 16-24. These rules define who contributes to the primary analysis. In general, excluding participants can change the population represented by an estimate, particularly if exclusion is related to follow-up or outcome status. The registry record does not report how many participants were excluded for each reason or how missing measurements were handled.

The record also does not report an intention-to-treat analysis, an imputation method, or a sensitivity analysis for missing data. A per-protocol definition alone does not explain how every incomplete measurement pattern was handled. The stated endpoint uses a time-adjusted average, but the record does not provide the calculation details or the rules for constructing that average when measurements are absent.

How should the planning illustrations be understood?

As a general statistical point, a sample-size planning illustration asks how many participants might be needed for a specified design and effect under stated assumptions. It is not an observed trial result, and it is not observed power. The planning assumptions described for this record include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The record says that the illustrated counts are participants per arm for non-time-to-event outcomes.

Those assumptions describe a hypothetical two-arm planning exercise, not the STABIL Study’s single-arm design. Its illustrations should not be read as the trial’s original design justification or as evidence about the observed endpoint. The registry record does not report the trial’s sample-size justification or say that the study was planned using those assumptions. Any sample-size illustration is therefore distinct from the enrolled 188 participants and from the unreported primary endpoint result.

What can the safety counts establish?

As a general statistical point, event counts describe how many participants had recorded events in the observed group. Without a concurrent control group, those counts do not establish whether the event frequency differs from another treatment or from the frequency that would have occurred otherwise. The registry lists 41 participants with a serious adverse event and 38 with another adverse event entry among 188 at risk in the C.E.R.A. group. It also lists six serious-event terms at 1.1% each. The record does not report the event-analysis methods, exposure-adjusted rates, or a comparative safety analysis.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("C.E.R.A.")
n      <- c(154)
events <- c(82)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  C.E.R.A.  154  82  53.2  45.0  61.3  45.4  61.0  45.4  61.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists seven outcome measures in total and describes the primary endpoint alongside secondary outcomes concerning hemoglobin, dose adjustment, transfusion, and anti-epoetin antibodies. It does not report a multiplicity strategy, such as an adjustment to account for testing several outcomes. The record also lists no analysis records. It is therefore not possible to determine from the registry record whether confirmatory testing was planned across outcomes or how any multiple comparisons were intended to be interpreted.

Missing-data handling is not reported in the registry record. The primary endpoint’s per-protocol population excludes participants with fewer than 3 recorded hemoglobin values, missing C.E.R.A. administrations, withdrawal, or inadequate iron status during Weeks 16-24. Those eligibility rules identify some exclusions, but do not specify how incomplete measurements among included participants were handled or whether additional sensitivity analyses were conducted. The number of participants excluded and the final analysis denominator are also not reported.

As a general statistical point, missingness can affect an estimate when participants with incomplete follow-up differ from those with complete data. Excluding participants may also make the analyzed group less representative of all enrolled participants. A transparent report typically states the denominator, the extent and reasons for missingness, and the assumptions behind any method used to address it. Those details are not reported in the registry record.

The record defines a per-protocol population for the primary outcome, but does not report an intention-to-treat analysis or another analysis population’s result. Consequently, the robustness of the primary estimate to different population definitions or missing-data assumptions cannot be assessed.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial fibrillation (1.1%), dyspepsia (1.1%), bronchitis (1.1%), catheter sepsis (1.1%), sepsis (1.1%).

The registry’s adverse-event summary lists 188 participants at risk in the C.E.R.A. group and 41 participants with a serious adverse event. It separately lists 188 participants at risk and 38 participants with another adverse event entry. The registry record does not explain the precise distinction between these two event summaries, so they should be read as separate listed counts rather than combined or treated as mutually exclusive categories.

Six serious-event terms are listed, each at 1.1%: atrial fibrillation, dyspepsia, bronchitis, catheter sepsis, sepsis, and arteriogram coronary. The registry record does not report the number of participants for each term in this summary, whether a participant could contribute more than one term, or the timing and duration of events. Death counts are not reported in the registry record.

As a general statistical point, counts and percentages describe events recorded in a study group; they do not alone establish that an intervention caused an event. With no concurrent control group in this study, these figures do not provide a like-for-like comparison of safety between treatments. The registry record does not report comparative safety estimates or exposure-adjusted event rates.

13. What the Result Does, and Does Not, Mean

The study’s primary question concerns maintenance of average hemoglobin during Week 17 up to Week 24 under monthly intravenous C.E.R.A. The endpoint combines a participant-specific stability criterion, within +/-1 g/dL of the reference value, with an absolute target range of 10.0 to 12.0 g/dL. The registry record explains how the reference was established and how the efficacy-period average was defined.

However, the numerical primary result is not reported in the registry record. Neither the percentage meeting the endpoint nor the limits of its 95% confidence interval are available in the record. It is therefore not possible to describe how many participants met the combined criterion, or how precisely that proportion was estimated, from this information.

The study’s single-arm, open-label design also limits interpretation. The registry describes outcomes among participants receiving C.E.R.A., not a randomized difference against another treatment. A participant’s own reference value is part of the endpoint, but it is not a substitute for a control group. The record cannot establish how outcomes would have differed under another treatment or without the study intervention.

The safety summary reports serious and other adverse-event counts, along with six serious-event terms at 1.1% each. These figures describe recorded events in the study group. They do not establish a causal relationship or comparative safety, and deaths are not reported in the registry record.

In short, the record supports an understanding of the trial design, its maintenance endpoint, its analysis-population definition, and selected safety counts. It does not report the primary endpoint result, the analysis denominator, or a comparative treatment estimate. Those absences limit conclusions about the observed extent and precision of hemoglobin maintenance and about how outcomes compare with other approaches.

14. Why This Trial Matters Statistically

This trial illustrates how an endpoint can combine a change relative to an individual reference with a clinically specified target range. The primary definition does not ask only whether hemoglobin stayed near baseline or only whether it fell within a target range; it requires both. That distinction matters when interpreting what a reported percentage would represent.

The design also shows why an internal reference and a concurrent comparator answer different questions. A participant’s reference value provides context for judging maintenance over time. A control group would support a between-group comparison under the study design. Because this study is single-arm, the registry record can describe the planned outcome among treated participants but cannot quantify a randomized comparative effect.

The per-protocol population definition is another important statistical feature. Excluding participants for missing measurements, missed administrations, withdrawal, or inadequate iron status affects which participants the primary estimate is intended to represent. Without the final denominator and the primary estimate, readers cannot assess how the exclusions shaped the reported outcome.

The record also demonstrates the difference between an endpoint definition and an endpoint result. It specifies the assessment period, reference measurements, target range, and confidence-interval measure, but does not report the numerical percentage or interval limits. A clear protocol question is not itself evidence of the observed outcome.

Finally, the planning illustrations described for this record use a hypothetical two-arm framework, whereas the trial is recorded as single-arm. This is a useful reminder that planning calculations depend on design assumptions and should not be mistaken for trial results, observed power, or evidence that the original study was adequately powered. The registry does not report the study’s own sample-size justification.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for interpretation is that the registry record does not report the primary endpoint estimate or its 95% confidence interval. It also does not report the number of participants included in the per-protocol analysis. The enrollment figure of 188 therefore cannot be assumed to be the primary endpoint denominator.

The study is single-arm and open-label, with no randomized comparator described. Consequently, the design does not provide a like-for-like control comparison, and outcomes cannot be attributed to the intervention through a randomized contrast. The record does not report masking or blinded outcome assessment; masking is listed as none.

The primary analysis excludes participants for several reasons, including fewer than 3 recorded hemoglobin values, missing administrations, withdrawal, and inadequate iron status during Weeks 16-24. The registry record does not give the number excluded for each reason, the final analysis population size, or the method used to handle other missing measurements. This limits assessment of how the analysis population relates to everyone enrolled.

The registry record does not report the analysis method for the confidence interval, a detailed statistical analysis plan, a multiplicity strategy, or an intention-to-treat result. It lists no analysis records. The record also does not provide detailed safety methods, exposure-adjusted rates, or death counts. These omissions constrain evaluation of precision, missing-data assumptions, outcome multiplicity, and comparative safety.

The brief summary describes an anticipated treatment duration of 3-12 months and dose selection based on prior epoetin use, but the record does not report treatment duration by participant or the distribution of starting doses. These details cannot be used to characterize actual exposure in the study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: STABIL Study: National Study With Mircera for Maintenance of Hemoglobin Level in Dialysis Patients — NCT00642850.
• Registry record last updated 2016-06-23; status last verified 2016-05.
• Results first posted 2016-06-23.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The STABIL Study (NCT00642850) is listed as a completed Phase 3, single-arm, open-label study of monthly intravenous C.E.R.A. In dialysis participants with chronic renal anemia. Enrollment was 188. The brief summary describes starting doses of 120, 200 or 360 micrograms according to the preceding epoetin dose, with anticipated treatment lasting 3-12 months.

The primary endpoint was the percentage of participants whose time-adjusted average hemoglobin during Week 17 up to Week 24 was within +/-1 g/dL of the reference value and within 10.0 to 12.0 g/dL. The primary analysis population was defined per protocol with listed exclusions. The primary percentage, confidence-interval limits, and final analysis denominator are not reported in the registry record.

The adverse-event summary lists 41 participants with a serious adverse event and 38 with another adverse event entry among 188 at risk in the C.E.R.A. group. Six serious-event terms are listed at 1.1% each. The record does not describe a randomized comparator or report a comparative treatment estimate.